Mechanisms involved in the blocking effects of pimozide on smooth muscle contraction

Pimozide, a dopamine-receptor antagonist, shifted to the right the concentration-response curves (CRC) induced by (-)-noradrenaline in the isolated posterior mesenteric artery of the cat. Since this antagonism could be related to a blockade of vascular alpha-adrenoceptors, we compared the effects of pimozide (0.20 microM) with those of phentolamine (0.31 microM). The onset of the blockade by pimozide on the (-)-noradrenaline-induced contractions was slower when compared with that of phentolamine. In addition, the effects of pimozide did not reverse by washing while those of phentolamine did. Pimozide but not phentolamine inhibited the contractions elicited by potassium and it decreased the maximum responses of the curves. This effect was partially reversed by CaCl2 10.2 mM. Pimozide displaced the CRC induced by CaCl2 to a greater extent than phentolamine. Even if a blocking effect on alpha-adrenoceptors cannot be discarded, our results suggest that pimozide may interfere with calcium in the arterial smooth muscle. Furthermore, vascular smooth muscle seems to be more sensitive than non-vascular tissue to the action of pimozide.